Avaliação preditiva estrutural das serino peptidases de aranhas: as relações evolutivas e de estrutura/função

Abstract

Serine peptidases (SP) are hydrolases represented in many living organisms, with chymotrypsins and trypsins being the main digestive SPs. Studies of genomes, transcriptomes and proteomes of spiders allow identifying these enzymes in different tissues and/or secretions of these animals and suggest that SPs are involved in poisoning and digestion, two very important processes for the evolutionary success of the group. In order to compare the SPs involved in these processes, in silico analyses of the databases of a total of 38 distinct species of spiders were performed, totaling 1,200 sequences of SPs. Proteomic analyses of Nephilingis cruentata, Stegodyphus mimosarum and Acanthoscurria geniculata show the presence of SPs in poisons (SPV) and digestive process (SPD). In general, the SPVs present a molecular mass in the range between 30 and 37 kDa and pI in the range of 4.65 and 9.79, presenting, in most sequences, only the catalytic domain. Fluid and digestive system SPDs mandatorily present the catalytic domain associated with CUB-LDLa, indicating that CUB-LDL SPcatalytic combination is a signature of the digestive SPs of spiders. These enzymes have a molecular mass of 36 to 140 kDa and pI between 4.4 and 5.6. Other differences found among SPV and SPD are: predicted patterns of glycosilation, cell addressing and structural prediction. Among the different digestive SPs there is a distinction between hydrophobicity, electrostatic potential, and substrate accessibility. Molecular docking also allowed predicting the interaction behavior of SPs with inhibitors that mimic substrates, as Kunitz type inhibitors. Analyses indicate that poison enzymes have greater accessibility of the catalytic triad to the substrate. Phylogenetic analyses show that the different groups of digestive SPs are represented in all studied spider species, keeping CUB-LDLa as a signature. The conservation of the CUB-LDLa domain was also observed in SPs of other Groups of Arachnida such as Scorpionidae, Acari and Opiliones, being even present in Limulus representative of the Chelicerata group. The association of these domains is possibly related to different functionalities of SPs in arachnids maintained throughout the evolutionary process.